Ironjustic
Sun, Nov-04-07, 17:15
A little data mining would have saved these guys some time ..
this was hypothesized and proven quite awhile ago.
<<snip>> high incidence rate of HFE gene mutations among MDS
patients <<snip>>
http://www3.interscience.wiley.com/cgi-bin/abstract/11429681-
8/ABSTRACT
Original Article Hemochromatosis-associated gene mutations in
patients with myelodysplastic syndromes with refractory anemia
with ringed sideroblasts Zachary P. Nearman 1, Hadrian Szpurka
1, Bianca Serio 1, Ilka Warshawksy 2, Karl Theil 2, Alan
Lichtin 3, Mikkael A. Sekeres 3, Jaroslaw P. Maciejewski 1 3 *
1Experimental Hematology and Hematopoiesis Section, Taussig
Cancer Center, Cleveland, Ohio 2Department of Clinical
Pathology, Cleveland Clinic, Cleveland, Ohio 3Department of
Hematologic Oncology and Blood Disorders, Taussig Cancer
Center, Cleveland Clinic, Cleveland, Ohio
email: Jaroslaw P. Maciejewski (maciejj@ccf.org)
*Correspondence to Jaroslaw P. Maciejewski, Experimental
Hematology and Hematopoiesis Section, Taussig Cancer Center
R-40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH
Abstract We observed increased ferritin levels in newly
diagnosed MDS-RARS patients without transfusional
iron-overload. Hence, we hypothesized RARS patients may harbor
hemochromatosis-related mutations, which could contribute to
the pathophysiology of this myelodysplastic syndromes (MDS)
subset. We studied a cohort of 140 MDS patients: 42 with RARS,
10 with increased ringed sideroblasts, and 96 with other forms
of MDS (43 RA, 27 RAEB, 17 RAEB-T, 8 MDS/MPD, 1 CMML).
Patients were genotyped using restriction fragment length
polymorphism, designed to detect C282Y and H63D mutations of
the HFE gene. We found significantly higher frequency of
heterozygosity for C282Y mutation in RARS patients compared
with a large control population of matched race individuals
(21 vs. 9.8% in controls, P =3D 0.03); H63D genotype was not
significantly increased. Frequency of HFE variation in other
MDS subtypes failed to differ significantly from controls.
Within this group, we included patients with a rare form of
MDS, provisionally subclassified by WHO as RARS with
thrombocytosis (RARSt). 10/14 RARSt patients were carriers of
either C282Y or H63D allele significantly increased compared
with the combined prevalence in a healthy population (71 vs.
33%, P < 0.01). We found expected distribution of mutant HFE
alleles in patients with other forms of MDS (9.1 vs. 9.8%, P
=3D 0.82). Increased prevalence of HFE gene mutations is not a
generalized feature of MDS, but some subgroups of MDS,
especially those characterized by excessive accumulation of
ringed sideroblasts, exhibit C282Y mutations at a higher
frequency than in other forms of MDS and healthy controls. Am.
J. Hematol., 2007. =A9 2007 Wiley-Liss, Inc.
Received: 9 April 2007; Accepted: 17 April 2007 Digital Object
Identifier (DOI)
10.1002/ajh.20995 About DOI
--------------------------------------------------------------
--------------=
-----
Acta Haematol. 2003;109(2):64-7. Related Articles, Links
High incidence of hemochromatosis gene mutations in the
myelodysplastic syndrome: the Budapest Study on 50 patients.
Varkonyi J, Tarkovacs G, Karadi I, Andrikovics H, Varga F,
Varga F, Demeter J, Tordai A.
3rd Department of Internal Medicine, Semmelweis University
Medical School, Budapest, Hungary. quit...@axelero.hu
Genotypic testing of nonselected patients with the
myelodysplastic syndrome
(MDS) for the C282Y and H63D mutations of the HFE gene
responsible for hereditary hemochromatosis revealed a
significantly increased frequency of these mutations
when compared to healthy blood donors reflecting the
average population. Among the 50 patients examined [26
refractory anemia (RA), 9 refractory anemia with ring
sideroblasts (RARS), 2 refractory anemia with excess of
blasts (RAEB) and 13 refractory anemia with excess of
blasts in transformation (RAEB-t)] there were 24
heterozygotes (20 for H63D and 4 for
C282Y), 1 homozygote for H63D and 1 compound heterozygote. The
difference between the HFE-positive and HFE-negative MDS
patients as regards initial serum iron and transferrin
saturation was not significant. Inevitably the iron
overload syndrome eventually develops in MDS patients
due to intrinsic characteristics of the disease as well
as an escalating need for blood transfusion therapy in
the course of the disease. The high incidence rate of
HFE gene mutations among MDS patients may also
contribute to this vicious circle. Copyright 2003 S.
Karger AG, Basel
PMID: 12624489 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
-------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
this was hypothesized and proven quite awhile ago.
<<snip>> high incidence rate of HFE gene mutations among MDS
patients <<snip>>
http://www3.interscience.wiley.com/cgi-bin/abstract/11429681-
8/ABSTRACT
Original Article Hemochromatosis-associated gene mutations in
patients with myelodysplastic syndromes with refractory anemia
with ringed sideroblasts Zachary P. Nearman 1, Hadrian Szpurka
1, Bianca Serio 1, Ilka Warshawksy 2, Karl Theil 2, Alan
Lichtin 3, Mikkael A. Sekeres 3, Jaroslaw P. Maciejewski 1 3 *
1Experimental Hematology and Hematopoiesis Section, Taussig
Cancer Center, Cleveland, Ohio 2Department of Clinical
Pathology, Cleveland Clinic, Cleveland, Ohio 3Department of
Hematologic Oncology and Blood Disorders, Taussig Cancer
Center, Cleveland Clinic, Cleveland, Ohio
email: Jaroslaw P. Maciejewski (maciejj@ccf.org)
*Correspondence to Jaroslaw P. Maciejewski, Experimental
Hematology and Hematopoiesis Section, Taussig Cancer Center
R-40, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH
Abstract We observed increased ferritin levels in newly
diagnosed MDS-RARS patients without transfusional
iron-overload. Hence, we hypothesized RARS patients may harbor
hemochromatosis-related mutations, which could contribute to
the pathophysiology of this myelodysplastic syndromes (MDS)
subset. We studied a cohort of 140 MDS patients: 42 with RARS,
10 with increased ringed sideroblasts, and 96 with other forms
of MDS (43 RA, 27 RAEB, 17 RAEB-T, 8 MDS/MPD, 1 CMML).
Patients were genotyped using restriction fragment length
polymorphism, designed to detect C282Y and H63D mutations of
the HFE gene. We found significantly higher frequency of
heterozygosity for C282Y mutation in RARS patients compared
with a large control population of matched race individuals
(21 vs. 9.8% in controls, P =3D 0.03); H63D genotype was not
significantly increased. Frequency of HFE variation in other
MDS subtypes failed to differ significantly from controls.
Within this group, we included patients with a rare form of
MDS, provisionally subclassified by WHO as RARS with
thrombocytosis (RARSt). 10/14 RARSt patients were carriers of
either C282Y or H63D allele significantly increased compared
with the combined prevalence in a healthy population (71 vs.
33%, P < 0.01). We found expected distribution of mutant HFE
alleles in patients with other forms of MDS (9.1 vs. 9.8%, P
=3D 0.82). Increased prevalence of HFE gene mutations is not a
generalized feature of MDS, but some subgroups of MDS,
especially those characterized by excessive accumulation of
ringed sideroblasts, exhibit C282Y mutations at a higher
frequency than in other forms of MDS and healthy controls. Am.
J. Hematol., 2007. =A9 2007 Wiley-Liss, Inc.
Received: 9 April 2007; Accepted: 17 April 2007 Digital Object
Identifier (DOI)
10.1002/ajh.20995 About DOI
--------------------------------------------------------------
--------------=
-----
Acta Haematol. 2003;109(2):64-7. Related Articles, Links
High incidence of hemochromatosis gene mutations in the
myelodysplastic syndrome: the Budapest Study on 50 patients.
Varkonyi J, Tarkovacs G, Karadi I, Andrikovics H, Varga F,
Varga F, Demeter J, Tordai A.
3rd Department of Internal Medicine, Semmelweis University
Medical School, Budapest, Hungary. quit...@axelero.hu
Genotypic testing of nonselected patients with the
myelodysplastic syndrome
(MDS) for the C282Y and H63D mutations of the HFE gene
responsible for hereditary hemochromatosis revealed a
significantly increased frequency of these mutations
when compared to healthy blood donors reflecting the
average population. Among the 50 patients examined [26
refractory anemia (RA), 9 refractory anemia with ring
sideroblasts (RARS), 2 refractory anemia with excess of
blasts (RAEB) and 13 refractory anemia with excess of
blasts in transformation (RAEB-t)] there were 24
heterozygotes (20 for H63D and 4 for
C282Y), 1 homozygote for H63D and 1 compound heterozygote. The
difference between the HFE-positive and HFE-negative MDS
patients as regards initial serum iron and transferrin
saturation was not significant. Inevitably the iron
overload syndrome eventually develops in MDS patients
due to intrinsic characteristics of the disease as well
as an escalating need for blood transfusion therapy in
the course of the disease. The high incidence rate of
HFE gene mutations among MDS patients may also
contribute to this vicious circle. Copyright 2003 S.
Karger AG, Basel
PMID: 12624489 [PubMed - indexed for MEDLINE]
--------------------------------------------------------------
-------------
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk